Funded Projects

Funded Projects

The Cancer Pathology Translational Research Grants will complement the education and training program available through the Network to increase molecular pathology and research knowledge amongst the pathologist in Ontario. To foster the development of this research community grantees and their trainees will present there work at the Network’s annual meeting, the Ontario Cancer Pathology Research Meeting.

The Role of the Transcriptional Regulator TBX3 in Early Breast Cancer Progression: a possible regulator of the transition from in situ (DCIS) to invasive mammary carcinoma (IMC)

This study is looking at biomarkers in tissue samples of people with Ductal Carcinoma In Situ (DCIS) to help tell which patients will develop invasive mammary carcinoma (an advanced form of breast cancer).

Ductal Carcinoma In Situ (DCIS) means cells inside some of the ducts of the breast have started to turn into cancer cells. These cells are inside the ducts and have not started to spread into the surrounding breast tissue. Doctors diagnose DCIS by looking at whether or not cells within the ducts of a patient’s tissue sample appear benign (non-cancerous) or malignant (cancerous). However, only some of these patients will go on to develop invasive breast cancer and it is currently difficult for doctors to tell which of these patients are at risk.

Researchers believe that increased activity of the T-box transcription factor (TBX3) gene is linked to more aggressive breast cancer. In this study researchers will assess which other genes are potentially regulated by TBX3, and will use tissue samples from current breast cancer patients to determine whether increased activity of this gene, and/or specific genes that this gene itself activates (such as Slug and Twist1) might be used as an indicator of the potential to break out of the ducts and invade adjacent breast tissue (i.e to become more aggressive).Researchers hope that one or more of these tests will help doctors predict which patients are at risk of progressing to advanced breast cancer.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research. Find out more about pathology or why molecular pathology is important in cancer research here [link].

Development of Pediatric OncoScan Genomic and SNP Array for clinical implementation

This study is looking at biomarkers in tissue samples of children with cancer to help diagnose their cancer and to tell which patients are more likely to respond to different available treatments.

Some pediatric (childhood) cancers develop as a result of changes in the genes’ code and/or the number of copies of the genes (gains or losses of the gene). Researchers believe understanding which changes have occurred in a child’s cancer can help to diagnose the cancer and to identify treatments to which the child is more likely to respond. In this study researchers will use a test normally used to for adult cancers and adapt this for children with cancer. Researchers will use tissue samples from current patients with childhood cancer to develop this test so that doctors can figure out which gene changes are present in an individual's cancer. Researchers hope that this test will help doctors to better match children with cancer to treatments.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research. Find out more about pathology or why molecular pathology is important in cancer research here [link].

This study is looking at biomarkers in tissue samples of people with early endometrial (womb) cancer to help tell which patients can avoid having surgery.

Endometrial cancers, which have not grown beyond the womb lining are considered localized, these can often be treated with surgery with or without radiotherapy. However surgery for these patients means partial (removal of the womb) or complete hysterectomy (removal of the womb and ovaries) and can be life-changing for patients wishing to have children or not possible for patients who cannot undergo surgery because of other health conditions.

Researchers believe that womb cancer patients with a change in a type of protein which regulates the hormone progesterone, could put these patients at higher risk of their tumour spreading. Patients with changes to this protein, called progesterone receptor isoforms, PR-A and PR-B, may respond better to a type of hormone therapy called progestin. In this study researchers will develop a test, using tissue samples from current womb cancer patients, which can be used to figure out if this type of protein change is present in an individual's cancer and what impact this has on their tumour spreading.

Researchers will also test whether patients with these protein changes respond better to progestin. Researchers hope that this test will help doctors predict which patients will need surgery and which patients can be given hormone therapy.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research. Find out more about pathology or why molecular pathology is important in cancer research here [link].

Kidney cancer includes multiple subtypes. Papillary renal cell carcinoma (PRCC), the cancer we are proposing this research for, is the second most common form of kidney cancer. However PRCC itself is divided into two subtypes, the PRCC type 1 and PRCC type 2. That is based upon the way they look under the microscope. Previous researches have noted that type 2 is usually a more aggressive form of cancer than type 1. As such patients with these cancers should be followed differently. Other studies as well as ours have found that the types have a different biology. Therefore their response to cancer drugs is expected to be different. However to date, they are treated by doctors as one entity.

Part of the dilemma is that nearly half the cases are hard to subtype using the microscope alone. There is a need for a test (biomarker) that can help Pathologist’s (cancer microscope doctors) distinguish between them. Our previous work identified some possible promising markers. We need to confirm these results in another set of cancer patients, which is part of our research proposal. The findings will help doctors divide patients properly in the right group for follow up and treatment.

Yet another confounding factor is that, even though the types are known to have different biology, the exact nature of these changes and how they affect the cancer response to drugs is not properly understood. Our previous research shows that the cancer types should respond differently to certain cancer drugs. We propose studying these differences further and assessing the response of the cancer cells (cancer cells made and grown for research, corresponding to our particular tumor types) to a number of current cancer medications. The results are expected to guide doctors into giving the patients, the right kind of medicine for the right kind of cancer.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research. Find out more about pathology or why molecular pathology is important in cancer research here [link].

This study is looking at biomarkers in tissue samples of people with gliomas (a type of brain tumour) to help tell which patients are more likely to respond to different treatments available.

Some gliomas develop as a result of changes in a patient’s genes or a number of different changes in different genes. Understanding which changes have occurred in a patient’s cancer can help to identify treatments which the patient is more likely to respond to.

Methylation is a process in which certain chemicals called ‘methyl groups’ are added to proteins, DNA and other molecules to make them active or inactive. Researchers believe that looking at where methyl groups have been attached can show which genes have been changed. Researchers will use tissue samples from current glioma patients to develop this pattern of methyl groups into a test so that doctors can figure out which gene changes are present in an individual's cancer. Researchers hope that this test will help doctors match patient with gliomas to treatments which target these changes.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research. Find out more about pathology or why molecular pathology is important in cancer research here [link].

This study is looking at biomarkers in tissue samples of people with endometrial (womb lining) cancer to determine which patients might respond to targeted therapies.

Endometrial cancers, which have not grown beyond the womb are considered localized. These can often be treated with surgery with or without radiotherapy. Cancers which have advanced beyond the womb are considered advanced and are less likely to respond to treatment.

Researchers believe that some patients with endometrial cancer have a specific genetic defect, in a gene called MLH1, and belong to a special category, called “Mismatch Repair-deficient”. In this study, researchers will develop a test, using tissue samples from current endometrial cancer patients, which can be used to figure out if this type of gene mutation is present in an individual's cancer and will allow doctors to determine if other family members are at also at increased risk for cancer.

Researchers also believe that patients with this type of gene mutation may respond better to a new and highly promising treatment called immunotherapy; so this test will also help doctors predict which patients might benefit from this treatment.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research. Find out more about pathology or why molecular pathology is important in cancer research here [link].

This study is looking at biomarkers in tissue samples of people with bladder cancer to help tell which patients are at risk of their cancer progressing.

Doctors diagnose bladder cancers by looking at how far cancer tumors have grown into the bladder. Most of these patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). This means the cancer is only in the innermost layer of the bladder lining or has started to grow into the connective tissue beneath the bladder lining. NMIBC can often be treated with surgery.

A small number these patients will progress to advanced bladder cancer. This means the cancer has started to grow beyond the bladder lining and into the surrounding muscle or other parts of the body. Half of these patients with advanced bladder cancer will have incurable disease.

Researchers believe that two gene networks, Sonic HedgeHog (SHH) and Bone Morphogenetic Protein (BMP), are linked to more aggressive bladder cancer when they are turned off. In this study researchers will develop a test, using tissue samples from current bladder cancer patients, which can be used to figure out if these networks are turned off in an individual's cancer. Researchers hope that this test will help doctors predict which patients are at risk of progressing to advanced bladder cancer.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research. Find out more about pathology or why molecular pathology is important in cancer research here [link].

This study is looking at genetic alterations in tissue samples of people with cancer of the cervix (the neck of the womb) to help tell which patients have a type of cervix cancer called gastric type endocervical adenocarcinomas, this means cervix cancers which contain mucin types similar to gastric (stomach) cancer.

Researchers believe that patients with gastric type endocervical adenocarcinoma are less likely to respond to treatment typically used for cervix cancer. Doctors diagnose cancer of the cervix by looking at whether or not cells within a patient’s tissue sample appear benign (normal) or malignant (cancerous) however it is currently difficult for doctors to tell which of these cervix cancer patients have gastric type endocervical adenocarcinoma.

Changes in a patient’s genes can be associated with different types of cancer. In this study researchers will use tissue samples from current cervix cancer patients to find out which changes in which genes are associated with patients who have gastric type endocervical adenocarcinoma.

Researchers will then develop a test which can be used to figure out if these genes are changed in new patients with cervix cancer. Researchers hope that this test will help to tell which of these cervix cancer patients have gastric type endocervical adenocarcinoma. Also they are hoping their findings might help in new targeted therapies for this type of cancer.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research. Find out more about pathology or why molecular pathology is important in cancer research here [link].

Ezrin as a novel biomarker for response to chemotherapy in breast cancer

This study is looking at biomarkers in tissue samples of people with breast cancer to help tell which patients will respond to chemotherapy.

Researchers believe that activity of a protein called ezrin can increase a patient’s risk of developing advanced breast cancer, which does not respond to chemotherapy. In this study researchers will develop a test, using tissue samples from current breast cancer patients, which can be used to figure out the level of activity of this protein in an individual's tissue sample and what impact this has on whether their cancer will respond to chemotherapy.

Researchers also believe that patients with a decreased level of ezrin protein activity may be more sensitive to two drugs called doxorubicin and paclitaxel. Researchers hope that this test will help doctors predict which patients will benefit from these treatments or a combination of these treatments.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research. Find out more about pathology or why molecular pathology is important in cancer research here [link].

Myeloid cancer diagnosis has historically relied on changes detected under the microscope, and limited, low-resolution genetic tests that take time to obtain. This has led to challenges with diagnosis, particularly for MDS, and mostly one-size-fits-all treatment. As myeloid cancers increase with age, we must do better to prepare for and serve our aging population.

Our strategy for Path2MyDx is to improve diagnosis and treatment options for myeloid cancer patients by advancing testing. We will utilize a “next-generation” sequencing (NGS) test that incorporates objective, personalized genetic information from DNA and RNA, with high throughput and a rapid turnaround time. In this way, we will build individual molecular pathology profiles that help clinicians to diagnose myeloid cancer earlier and more precisely, while better informing patient risk and guiding treatment decisions. Beyond diagnosis, we also believe NGS will help clinicians monitor and fine-tune treatment in real time, to better manage patients with myeloid cancers. Finally, we will learn from this pilot, share our knowledge with other centers, and advocate for this NGS test to be funded by government.

This study aims to identify new markers of aggressiveness in tissue samples of patients with meningiomas (a type of brain tumour). Although many patients with meningiomas do well following surgery, some tumours recur and can behave very aggressively. These types of meningiomas are referred to as clinically malignant meningiomas. It is important identify clinically malignant meningiomas as they have significant implications to a patient’s expected outcome and treatment plan.

Doctors have traditionally made predictions regarding the biological behavior of meningiomas based on specific features seen under the microscope. It has however proven difficult to accurately predict when meningiomas will behave aggressively and return after surgery using this tool. Identification of better predictors of clinically aggressive meningiomas are thus needed.

As has now been shown in many cancer types, “molecular” analysis of meningiomas may help better predict their biological behavior. Specifically, for this project, using a technology known as mass spectrometry (MS), the global protein makeup (proteome) of tumors will be analyzed. Because proteins, the products of genes, are directly responsible for carrying out most of a cell’s function, their levels are thought to be a strong measure of biological activity. Analyzing the protein differences between benign and cancerous meningiomas may thus allow the discovery of new markers that can better predict the likelihood that a meningioma is malignant. In this study, researchers will analyze meningioma tissue samples from patients with either benign and malignant behavior in attempts to find protein patterns specific to each type.

Researchers believe that patients with a protein pattern indicative of an aggressive meningiomas can benefit from radiotherapy after surgery to help prevent tumor recurrence. Researchers hope that this test will help doctors predict which patients will benefit from this additional treatment and which patients will not. This will also help provide reassurance and prevent over-treatment of patients will less aggressive meningiomas. Lastly, analysis of the protein make-up of meningiomas may also help identify new less-invasive and less-toxic therapeutic targets for all patients suffering from meningiomas.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research. Find out more about pathology or why molecular pathology is important in cancer research here [link].

OMPRN drives new innovations in cancer research

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